{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T19:39:17Z","timestamp":1769974757618,"version":"3.49.0"},"reference-count":77,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T00:00:00Z","timestamp":1485820800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2017,1,30]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Periconception maternal nutrition and folate in particular are important factors influencing the incidence of neural tube defects (NTDs). Many but not all NTDs are prevented by folic acid supplementation and there is a pressing need for additional strategies to prevent these birth defects. Other micronutrients such as iron are potential candidates, yet a clear role for iron deficiency in contributing to NTDs is lacking. Our previous studies with the <jats:italic>flatiron<\/jats:italic> (<jats:italic>ffe<\/jats:italic>) mouse model of Ferroportin1 (Fpn1) deficiency suggest that iron is required for neural tube closure and forebrain development raising the possibility that iron supplementation could prevent NTDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We determined the effect of periconception iron and\/or folic acid supplementation on the penetrance of NTDs in the <jats:italic>Fpn1<jats:sup>ffe<\/jats:sup><\/jats:italic> mouse model. Concurrently, measurements of folate and iron were made to ensure supplementation had the intended effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High levels of iron supplementation significantly reduced the incidence of NTDs in <jats:italic>Fpn1<jats:sup>ffe<\/jats:sup><\/jats:italic> mutants. <jats:italic>Fpn1<\/jats:italic> deficiency resulted in reduced folate levels in both pregnant dams and embryos. Yet folic acid supplementation did not prevent NTDs in the <jats:italic>Fpn1<jats:sup>ffe<\/jats:sup><\/jats:italic> model. Similarly, forebrain truncations were rescued with iron. Surprisingly, the high levels of iron supplementation used in this study caused folate deficiency in wild\u2010type dams and embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that iron supplementation can prevent NTDs and forebrain truncations in the <jats:italic>Fpn1<jats:sup>ffe<\/jats:sup><\/jats:italic> model. Surprisingly, high levels of iron supplementation and iron overload can cause folate deficiency. If iron is essential for neural tube closure, it is possible that iron deficiency might contribute to NTDs. Birth Defects Research 109:81\u201391, 2017. \u00a9 2016 The Authors Birth Defects Research Published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23542","type":"journal-article","created":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T19:35:40Z","timestamp":1482608140000},"page":"81-91","source":"Crossref","is-referenced-by-count":9,"title":["High levels of iron supplementation prevents neural tube defects in the <i>Fpn1<sup>ffe<\/sup><\/i> mouse model"],"prefix":"10.1002","volume":"109","author":[{"given":"Bethany A.","family":"Stokes","sequence":"first","affiliation":[{"name":"Department of Biology The George Washington University Washington DC"},{"name":"Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia A.","family":"Sabatino","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Research, Children's 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